1. Field of the Invention
The invention relates to insect pheromones and their synthesis, particularly methods of synthesizing Z-alkenyl insect pheromones.
2. Description of the Related Art
Insects use sex pheromones as a form of chemical communication to attract members of the opposite sex in order to engage in reproduction. Increasingly, synthetic insect sex pheromones are used as eco-friendly alternatives to conventional pesticides. They have been used in attract-and-kill, mating disruption, mass trapping, and insect monitoring approaches to pest control, and offer a number of advantages over conventional pesticides: they only affect the targeted species, they are typically not environmentally persistent, and the target insect does not develop resistance to the treatment.
The sex pheromones produced by female moths (Lepidoptera) are complex mixtures of straight chain acetates, alcohols, and aldehydes, typically 10-18 carbons in length, with one-three double bonds. It has been stated that this class of pheromones, Type I, according to Ando's classification scheme (Ando T. et al., “Lepidopteran sex pheromones,” Top Curr Chem 239: 51-96, 2004) accounts for roughly 75% of the known pheromones. Another class of pheromones, Type II (15%), comprises polyunsaturated hydrocarbons and epoxy derivatives with long, straight chains (C17-C23).
One example of a Type I insect sex pheromone is (Z,Z)-11,13-hexadecadienal (HDAL). HDAL has been identified as the primary component of the sex pheromones of the navel orangeworm (Amyelois tranitella)—a significant crop pest—and the meal moth (Pyralis farinalis)—which infests grains and other dry foodstuffs. A method of synthesizing HDAL in seven or more steps was described as early as 1980 (Sonnett, P. E. and R. R. Heath, “Stereospecific synthesis of (Z,Z)-11,13-hexadienal, a female sex pheromone of the navel orangeworm, Amyelosis transitella, (Lepidoptera:Pyralidae)” Journal of Chemical Ecology, 6,221-228, 1980). U.S. Pat. Nos. 4,198,533 and 4,228,093 describe similar seven or more reaction step methods. An improved synthesis of HDAL is described in U.S. Pat. No. 8,115,035.
A traditional route to accessing Z-alkenes is semi-hydrogenation of alkynes, using hydrogen gas and a Lindlar-type catalyst. Lindlar-type catalysts typically consists of palladium metal deposited on calcium carbonate or barium sulfate, with a “catalyst poison,” such as lead acetate or lead oxide, added to deactivate some of the palladium active sites. Homogeneous catalysts can also be used. Traditional semi-hydrogenation has certain benefits, including low-cost reagents, reusable catalysts, high selectivity for Z isomers, clean (efficient) reactions, and a proven track record in the petroleum and fine chemicals industries. Unfortunately, the method also suffers from a number of drawbacks: Hydrogenation processes using heterogeneous catalysts can be challenging to scale; catalyst cost and availability are problematic; specialized equipment is required; the scope of viable substrates is limited; and the use of lead additives poses environmental problems.
In an effort to determine whether traditional semihydrogenation of diynes could be a viable route to (Z,Z)-1,3-dienes found in many insect pheromones, the present applicant undertook a detailed study of catalysts and conditions for the following reaction:

The applicant screened 22 catalysts and 22 solvents under a variety of reaction conditions, including different hydrogen pressures, different reaction times, different catalyst poisons, and several different hydrogen sources. A total of ca. 180 data points were collected over the course of more than 100 different reactions. The best result achieved was 60% conversion (alkyne to alkene), 52% desired product (the Z,Z isomer). From this, the applicant discerned that traditional semihydrogenation of alkynes is not a commercially viable route to this particular Z, Z-alkenyl insect pheromone backbone.
An alternate approach to semireduction of alkynes is described in Lalic, G., et al., “Monophasic Catalytic System for the Selective Semireduction of Alkynes,” Organic Letters, Vol. 15, No. 5, 1112-1115, 2013. The approach uses a copper catalyst (e.g., ICyCuOtBu, IPrCuOtBu, IMesCuOtBu, etc.), a silane, and an alcohol to semi-reduce an alkyne to a Z-alkene with high stereoselectivity. The reference provides little or no guidance for the semireduction of long-chain (>C12) alkynes, mixed alkyne-alkene compounds (other than 1,3-terminal enynes), or alkynes bearing specific functional groups of interest in the manufacture of insect pheromones. Lalic et al. do not describe a method for making insect pheromones or pheromone precursors by this semireduction protocol.